rs761185718

Variant names:

• chr19-55014192-C-CGGGA
• rs761185718
• ENST00000310373.7:c.1752_1753insTCCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001083899.2(GP6):​c.1752_1753insTCCC​(p.Gly585SerfsTer7) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00592 in 152,220 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00072 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: GP6 NM_001083899.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.268
• Publications: 2 publications found

Genes affected

GP6 (HGNC:14388): (glycoprotein VI platelet) This gene encodes a platelet membrane glycoprotein of the immunoglobulin superfamily. The encoded protein is a receptor for collagen and plays a critical role in collagen-induced platelet aggregation and thrombus formation. The encoded protein forms a complex with the Fc receptor gamma-chain that initiates the platelet activation signaling cascade upon collagen binding. Mutations in this gene are a cause of platelet-type bleeding disorder-11 (BDPLT11). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

GP6-AS1 (HGNC:55305): (GP6 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 19-55014192-C-CGGGA is Benign according to our data. Variant chr19-55014192-C-CGGGA is described in ClinVar as Benign. ClinVar VariationId is 777546.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00592 (901/152220) while in subpopulation AFR AF = 0.0209 (870/41530). AF 95% confidence interval is 0.0198. There are 11 homozygotes in GnomAd4. There are 435 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083899.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	NM_016363.5	MANE Select	c.*728_*729insTCCC		3_prime_UTR	Exon 8 of 8	NP_057447.5	Q9HCN6-1
	GP6	NM_001083899.2		c.1752_1753insTCCC	p.Gly585SerfsTer7	frameshift	Exon 8 of 8	NP_001077368.2	Q9HCN6-3
	GP6	NM_001256017.2		c.*728_*729insTCCC		3_prime_UTR	Exon 7 of 7	NP_001242946.2	Q9HCN6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GP6	ENST00000310373.7	TSL:1	c.1752_1753insTCCC	p.Gly585SerfsTer7	frameshift	Exon 8 of 8	ENSP00000308782.3	Q9HCN6-3
	GP6	ENST00000417454.5	TSL:1 MANE Select	c.*728_*729insTCCC		3_prime_UTR	Exon 8 of 8	ENSP00000394922.1	Q9HCN6-1
	GP6	ENST00000333884.2	TSL:1	c.*728_*729insTCCC		3_prime_UTR	Exon 7 of 7	ENSP00000334552.2	Q9HCN6-2

Frequencies

GnomAD3 genomes AF: 0.00594 AC: 903 AN: 152102 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00125 AC: 185 AN: 147996 AF XY: 0.000919

Gnomad AFR exome AF: 0.0200

Gnomad AMR exome AF: 0.000872

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000335

Gnomad OTH exome AF: 0.000228

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000722 AC: 413 AN: 571810 Hom.: 1 Cov.: 6 AF XY: 0.000543 AC XY: 168 AN XY: 309542

African (AFR) AF: 0.0191 AC: 318 AN: 16612

American (AMR) AF: 0.00102 AC: 36 AN: 35300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20102

East Asian (EAS) AF: 0.00 AC: 0 AN: 33070

South Asian (SAS) AF: 0.00 AC: 0 AN: 63394

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3908

European-Non Finnish (NFE) AF: 0.0000421 AC: 14 AN: 332868

Other (OTH) AF: 0.00143 AC: 45 AN: 31378

GnomAD4 genome AF: 0.00592 AC: 901 AN: 152220 Hom.: 11 Cov.: 32 AF XY: 0.00585 AC XY: 435 AN XY: 74420

African (AFR) AF: 0.0209 AC: 870 AN: 41530

American (AMR) AF: 0.00131 AC: 20 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68016

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00289 Hom.: 2

Bravo AF: 0.00646

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	GP6-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.27
Mutation Taster		=155/45	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs761185718; hg19: chr19-55525560;